Breast Brachytherapy Doubles Mastectomy Risk

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.